We have demonstrated that alpha-haloalkyl ketoximes can function as selective alkylating agents in biological systems. Our current research is progressing along four paths. 1) We are continuing to delineate reactivity patterns in the alkylation of protein functional groups with aryl alpha-haloalkyl ketoximes and related derivatives. These patterns should be helpful in developing the use of ketoximes as selective biological alkylating agents. 2) It has been suggested that the mode of action of tumor inhibitors like taxodone and vernolepin may involve the selective alkylation of certain protein sulfhydryl groups. Thus, a number of the alpha-haloalkyl oxime derivatives which we have demonstrated to posses marked selectivity in the alkylation of sulfhydryl groups in enzymes have been sent by us to NCI for testing of their antitumor activity, and we plan to continue actively to furnish NCI with such compounds. 3) While we have obtained kinetic evidence for the intermediacy of alpha-nitrosostyrene in those nucleophilic reactions of alpha-haloacetophenone oximes proceeding through an elimination-addition route, direct detection of such intermediates remains an objective for future research. Also, the possibility that species like alpha-nitrosostyrene formed by elimination from alpha-haloalkyl ketoximes can be trapped in cyclo addition reactions will be investigated from both the mechanistic and synthetic standpoints. 4) Finally, we are involved deeply in investigating the potential application of the chemistry of alpha-haloalkyl ketoximes in facilitating peptide synthesis by the solid phase method.